The present invention relates to a composition, a dialysis formulation, comprising trace elements. Especially, the dialysis formulation comprises selenium. The dialysis formulations are intended for dialysis treatment.
Dialysis is a well-established treatment technique for patients having kidney malfunction. The dialysis treatment artificially replaces some of the functions of the kidney. The dialysis treatment may be of different kinds, such as hemodialysis (intermittent or continuous) or peritoneal dialysis.
During dialysis treatment the blood is forwarded to a dialyzer (or filter, etc) and uremic toxins in the blood are removed. However, also the levels of other components in the blood are affected by the dialysis treatment. Trace elements are a group of essential substances that are present in minute quantities in the human body necessary for life. They have the capability to work both as antioxidants by being a co-factor, or being a part of essential enzymes, or by being able to induce oxidative stress by their chemical properties.
Regarding trace elements there are no general principles of how they are affected by dialysis therapy. Studies have shown that some trace elements, like chromium, copper and manganese are higher in dialysis patients, pre-dialysis compared to healthy subjects, due to ureamic conditions. Dialysis treatment is not efficient in respect of these trace elements and the levels of the trace elements are therefore raised. For some other trace elements are there indications that the levels instead are decreased, both pre-dialysis and during dialysis treatment. In addition, even if some trace element levels rise or decrease during a dialysis treatment, are the start level (pre-dialysis) often altered (higher or lower) compared with a healthy person, due to decreased or increased removal over time.
Zima, T. et al., Blood Purif 1999; 17:187-198, ‘Trace Elements in End-Stage Renal Disease’, indicates that the amount of trace elements may change during dialysis treatment. Regarding selenium, it is herein described that selenium deficiency is to be suspected and supplementation may thereof be beneficial.
Tonelli, M. et al., BMC Medicine 2009, 7:25, ‘Trace elements in hemodialysis patients: a systemic review and meta-analysis.’ describes that the level of the trace elements selenium, zinc, and manganese is lower in patients undergoing haemodialysis treatment when compared with normal and healthy control species. Herein it is also indicated that the dialysate concentration of trace elements are routinely not measured and/or manipulated.
Also Gidden, H. et al., Trans Am Soc Artif Intern Organs 1980; Vol XXVI, 133-138, describes the change of trace elements during dialysis treatment. The movement of the trace elements are described to depend on the metal-protein binding constant.
Cano, N. J. M., et al., Clinical Nutrition 28 (2009) 401-414, *ESPEN Guidelines on Parenteral Nutrition: Adult Renal Failure’, and Singer, P., et al., Clinical Nutrition 28 (2009) 387-400, ‘ESPEN Guidelines on Parenteral Nutrition: Intensive Care’ provide guidelines on parenteral nutrition to be applied in adult renal failure and intensive care, respectively. Micronutrients like trace elements are added to nutrient mixtures for parenteral administration.
US 2008/0015487 describe dialysis fluids comprising trace elements. However, this document only describes presence of trace elements in general in dialysis fluids. There is no indication that there is a need to be selective in the administration of trace elements to the dialysis patient.
There are no dialysis products available where it is possible to be selective in the choice of trace element. There are products for i.v. infusion available on the market containing a palette of trace elements, for example Tracel® and Decan®. Tracel® contains Cr3+, Cu2+, Fe3+, Mn2+, Zn2+, F−, I−, MoO42−, and SeO32− (according to its Summary Product Characteristics, SPC). In a similar way, the Decan® contains Fe, Zn, Cu, Mn, F, Co, I, Se, Mo, and Cr (according to its SPC). However, these trace elements are always delivered in combinations of trace elements to the subject in need thereof. According to the SPC's for those two products, there is a need to investigate the blood levels of manganese during long time use, i.e. more than four weeks.
Selenase® is a solution comprising selenium in form of selenite. It is intended to be used via infusion or injection to patients having selenium deficiency.
There is a need to replace the selenium when deficiency of selenium occurs. Especially, there is a need to replace selenium lost during the dialysis treatment and there is a need for formulations for dialysis treatment comprising selenium.
There are dialysis fluids available suitable for profiling or manipulation of different components removed or decreased in amount during dialysis. However, there are no dialysis products available where it is possible to be selective in the choice of trace element.
The purpose of the invention illustrated herein is to maintain physiological level of the trace elements which are decreased during the dialysis treatment. It has been shown that some trace elements are decreasing during dialysis treatment, while the level of some others are left unchanged, and some others are increasing or accumulated during the dialysis treatment.
Therefore, with the trace element containing products available today there is no possibility to replace individual trace elements, for example the trace elements that are lost during the dialysis treatment.
With a dialysis formulation comprising selenium and, optionally rubidium it is possible to manipulate and make sure that a proper dosage of those trace elements is given.